Transcriptional regulation of plasminogen activator inhibitor-1 by transforming growth factor-β, activin A and microphthalmia-associated transcription factor

Murakami, Masaru; Ikeda, Teruo; Saito, Taiju; Ogawa, Kenji; Nishino, Yoshinori; Nakaya, Kohei; Funaba, Masayuki

doi:10.1016/j.cellsig.2005.04.010

Cited by 30 publications

(21 citation statements)

References 40 publications

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“…5C, no difference in the slope of the curve was found for CAR mRNA of NMuMG cells treated with or without TGF-h, indicating that TGF-h does not affect CAR mRNA stability. Activation of TGF-h signaling by the ectopically added TGF-h was confirmed by measuring PAI-1 mRNA levels, as they are reported to be enhanced following TGF-h stimulation (30). The mRNA of c-myc was reported to be very unstable (34), thus being a suitable positive control for the efficacy of the actinomycin D applied (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…TGF-h elicits many of its cellular effects through transcriptional repression or activation of target genes through the Smad signaling cascade. For example, PAI-1 is strongly activated in response to TGF-h treatment (30), whereas the E-cadherin gene can be transcriptionally repressed by TGF-h as cells undergo EMT. The latter effect has been shown to be mediated through the transcriptional repressors snail and SIP1 (31,32).…”

Section: Resultsmentioning

confidence: 99%

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Transforming Growth Factor-β Receptor Inhibition Enhances Adenoviral Infectability of Carcinoma Cells via Up-Regulation of Coxsackie and Adenovirus Receptor in Conjunction with Reversal of Epithelial-Mesenchymal Transition

Lacher¹,

Tiirikainen

Saunier³

et al. 2006

Cancer Research

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Expression of the Coxsackie and Adenovirus Receptor (CAR) is frequently reduced in carcinomas, resulting in decreased susceptibility of such tumors to infection with therapeutic adenoviruses. Because CAR participates physiologically in the formation of tight-junction protein complexes, we examined whether molecular mechanisms known to down-regulate cellcell adhesions cause loss of CAR expression. Transforming growth factor-B (TGF-B)-mediated epithelial-mesenchymal transition (EMT) is a phenomenon associated with tumor progression that is characterized by loss of epithelial-type cell-cell adhesion molecules (including E-cadherin and the tight junction protein ZO-1), gain of mesenchymal biochemical markers, such as fibronectin, and acquisition of a spindle cell phenotype. CAR expression is reduced in tumor cells that have undergone EMT in response to TGF-B. This downregulation results from repression of CAR gene transcription, whereas altered RNA stability and increased proteasomal protein degradation play no role. Loss of CAR expression in response to TGF-B is accompanied by reduced susceptibility to adenovirus infection. Indeed, treatment of carcinoma cells with LY2109761, a specific pharmacologic inhibitor of TGF-B receptor types I and II kinases, resulted in increased CAR RNA and protein levels as well as improved infectability with adenovirus. This was observed in cells induced to undergo EMT by addition of exogenous TGF-B and in those that were transformed by endogenous autocrine/paracrine TGF-B. These findings show down-regulation of CAR in the context of EMT and suggest that combination of therapeutic adenoviruses and TGF-B receptor inhibitors could be an efficient anticancer strategy. (Cancer Res 2006; 66(3): 1648-57)

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Transforming Growth Factor-β Receptor Inhibition Enhances Adenoviral Infectability of Carcinoma Cells via Up-Regulation of Coxsackie and Adenovirus Receptor in Conjunction with Reversal of Epithelial-Mesenchymal Transition

Lacher¹,

Tiirikainen

Saunier³

et al. 2006

Cancer Research

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“…HMB45, Mart1, and MITF are now commonly used as immunohistochemical stains of the melanocytic lineage for melanoma diagnosis. Many additional MITF target genes have been identified, with some notable ones including Melastatin (TRPM1) (Miller et al 2004;Zhiqi et al 2004), AIM1 (ocular albinism 4 gene) (Du and Fisher 2002), Ocular albinism 1 gene (OA1) (Vetrini et al 2004), VMD2 (Esumi et al 2004), HIF1a (Busca et al 2005), and Plasminogen activator inhibitor-1 (Murakami et al 2006); a variety of mast cell genes including Prostaglandin D2; multiple mast cell proteases; adhesion molecules; and others (Ito et al 2004;Morii et al 2004;Takeda et al 2006).…”

Section: Mitf-melanocyte Master Regulatormentioning

confidence: 99%

Melanoma: from mutations to medicine

et al. 2012

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Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field—breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many—sometimes-related, although also distinct—biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field.

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“…Pigmentation-associated transcriptional targets of MITF include the pigment enzyme genes tyrosinase, TRP1, TRP2/Dct, which were recognized to contain an evolutionarily conserved consensus promoter/enhancer element that matches the MITF recognition sequence (Bentley et al 1994;Hemesath et al 1994;Yasumoto et al 1994). Additional differentiation-associated genes include Pmel17/silver/gp100 (which encodes the melanoma diagnostic epitope HMB45) (Halaban et al 1996;Baxter and Pavan 2003;Du et al 2003), MelanA/Mart1 , Melastatin (TRPM1) (Miller et al 2004;Zhiqi et al 2004), AIM1 (ocular albinism 4 gene) (Du and Fisher 2002), Ocular albinism 1 gene (OA1) (Vetrini et al 2004), VMD2 (Esumi et al 2004), HIF1␣ (Busca et al 2005), Plasminogen activator inhibitor-1 (Murakami et al 2006), numerous mast cell targets of MITF including Prostaglandin D2, multiple mast cell genes including proteases, various adhesion molecules and others (see Ito et al 2004;Morii et al 2004;Takeda et al 2006 and references therein), and melanocortin 1 receptor (MC1R) in mast cells and possibly in melanocytes (Adachi et al 2000;Smith et al 2001;Aoki and Moro 2002). Numerous additional genes are being identified through expression microarrays, and are liable to reflect the multiple steps involved between signaling, expressing, packaging, and exporting pigment.…”

Section: Transcriptional Targets Of Mitfmentioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

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Transcriptional regulation of plasminogen activator inhibitor-1 by transforming growth factor-β, activin A and microphthalmia-associated transcription factor

Cited by 30 publications

References 40 publications

Transforming Growth Factor-β Receptor Inhibition Enhances Adenoviral Infectability of Carcinoma Cells via Up-Regulation of Coxsackie and Adenovirus Receptor in Conjunction with Reversal of Epithelial-Mesenchymal Transition

Transforming Growth Factor-β Receptor Inhibition Enhances Adenoviral Infectability of Carcinoma Cells via Up-Regulation of Coxsackie and Adenovirus Receptor in Conjunction with Reversal of Epithelial-Mesenchymal Transition

Melanoma: from mutations to medicine

Malignant melanoma: genetics and therapeutics in the genomic era

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